Ravenscroft Neil, Omar Aneesa, Hlozek Jason, Edmonds-Smith Cesarina, Follador Rainer, Serventi Fabio, Lipowsky Gerd, Kuttel Michelle M, Cescutti Paola, Faridmoayer Amirreza
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Carbohydr Res. 2017 Oct 10;450:19-29. doi: 10.1016/j.carres.2017.08.006. Epub 2017 Aug 18.
Streptococcus pneumoniae is a globally important encapsulated human pathogen with approximately 100 different serotypes recognized. Serogroup 23 consists of serotype 23F, present in licensed vaccines, and emerging serotypes 23A and 23B. Here, we report the previously unknown structures of the pneumococcal capsular polysaccharides serotype 23A and 23B determined using genetic analysis, NMR spectroscopy, composition and linkage analysis and Smith degradation (of polysaccharide 23A). The structure of the serotype 23A capsular polysaccharide is: →4)-β-D-Glcp-(1→3)-[[α-L-Rhap-(1→2)]-[Gro-(2→P→3)]-β-D-Galp-(1→4)]-β-L-Rhap-(1→. This structure differs from polysaccharide 23F as it features a disaccharide backbone and the di-substituted β-Gal is linked to β-Rha as a side chain. This is due to the different polymerization position catalysed by the unusually divergent repeat unit polymerase Wzy in the 23A cps biosynthesis locus. Steric crowding in 23A, confirmed by molecular models, causes the NMR signal for H-1 of the di-substituted 2,3-β-Gal to resonate in the α-anomeric region. The structure of the serotype 23B capsular polysaccharide is the same as 23F, but without the terminal α-Rha: →4)-β-D-Glcp-(1→4)-[Gro-(2→P→3)]-β-D-Galp-(1→4)-β-L-Rhap-(1→. The immunodominant terminal α-Rha of 23F is more sterically crowded in 23A and absent in 23B. This may explain the reported typing cross reactions for serotype 23F: slight with 23A and none with 23B.
肺炎链球菌是一种在全球范围内具有重要意义的、有荚膜的人类病原体，已识别出约100种不同血清型。23血清群由23F血清型（存在于已获许可的疫苗中）以及新出现的23A和23B血清型组成。在此，我们报告了通过遗传分析、核磁共振光谱、组成和连接分析以及（对多糖23A的）史密斯降解法确定的肺炎球菌荚膜多糖血清型23A和23B此前未知的结构。血清型23A荚膜多糖的结构为：→4)-β-D-葡萄糖-(1→3)-[[α-L-鼠李糖-(1→2)]-[甘油-(2→磷酸→3)]-β-D-半乳糖-(1→4)]-β-L-鼠李糖-(1→。该结构与多糖23F不同，其特征在于具有二糖主链，且二取代的β-半乳糖作为侧链与β-鼠李糖相连。这是由于23A cps生物合成位点中异常不同的重复单元聚合酶Wzy催化的聚合位置不同。分子模型证实，23A中的空间拥挤导致二取代的2,3-β-半乳糖的H-1核磁共振信号在α-异头物区域共振。血清型23B荚膜多糖的结构与23F相同，但没有末端的α-鼠李糖：→4)-β-D-葡萄糖-(1→4)-[甘油-(2→磷酸→3)]-β-D-半乳糖-(1→4)-β-L-鼠李糖-(1→。23F的免疫显性末端α-鼠李糖在23A中空间拥挤程度更高，在23B中不存在。这可能解释了所报道的血清型23F的分型交叉反应：与23A有轻微交叉反应，与23B无交叉反应。
